Meropenem, one of the carbapenem antibiotics, has the following formula 1; and the chemical name thereof is (4R,5S,6S)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-6-((R)-1-hydroxyeth yl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid. Meropenem is clinically used in a trihydrate form, i.e., meropenem trihydrate (meropenem.3H2O).

U.S. Pat. No. 4,888,344 has disclosed a process for preparing a crystalline meropenem trihydrate, which comprises dissolving non-crystalline meropenem in water at 30° C., cooling the solution in a water bath (whereupon precipitation of a small amount of crystals), and adding acetone to the mixture to form a precipitate. As an improved process, WO 2007/031858 has disclosed a process for preparing meropenem trihydrate, which comprises dissolving meropenem or its hydrate in water in the presence of a base such as ammonia, optionally filtering through micron filter, adjusting the pH to 4.0 to 7.0 with an acid such as formic acid, and adding solvent (anti-solvent) to yield meropenem trihydrate. However, the process disclosed in U.S. Pat. No. 4,888,344 includes heating in the dissolving step, which causes forming degradation products, thereby resulting in unsatisfactory purity and low yield of the product, i.e., meropenem trihydrate. And also, the process disclosed in WO 2007/031858 includes additional steps for using a base and adjusting the pH with an acid, which makes the process complicated. In addition, the process disclosed in WO 2007/031858 may cause unwanted residual substances (for example, salts originated from acid-base reaction, fine dusts during the pH adjustment, metallic foreign substances, etc.) in the product.
In addition, WO 2011/141847 has disclosed a process for preparing meropenem trihydrate, which comprises dissolving non-sterile meropenem trihydrate in cold methanol to obtain a clear solution, optionally treating with carbon and/or filtering through micron filter, and adding an anti-solvent thereto. However, in order to obtain the clear solution in cold methanol, it is required to use excessive amounts of methanol. That is, in order to completely dissolve meropenem in cold (about 0° C.) methanol, it is required to use at least 8 times of methanol based on the weight of meropenem (for example, 80 ml of methanol based on 10 g of meropenem). If heating is carried out in order to avoid using the excessive amounts of methanol, degradation products of meropenem are formed, which results in lowering purity of the product. Moreover, the use of excessive amounts of methanol remarkably increases the amount of the anti-solvent used, which makes it difficult to apply the process to industrial mass production. Especially, the use of excessive amounts of both methanol and the anti-solvent causes a problem of high amounts of residual solvents in the product, i.e., meropenem trihydrate.